Bone marrow-derived immune cells mediate sensitization to liver injury in a myeloid differentiation factor 88-dependent fashion

I. Hritz, Arumugam Velayudham, Angela Dolganiuc, Karen Kodys, Pranoti Mandrekar, Evelyn Kurt-Jones, G. Szabó

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Toll-like receptors (TLRs) expressed on both immune cells and hepatocytes recognize microbial danger signals and regulate immune responses. Previous studies showed that TLR9 and TLR2 mediate Propionibacterium acnes-induced sensitization to lipopolysaccharide-triggered acute liver injury in mice. Ligand-specific activation of TLR2 and TLR9 are dependent on the common TLR adaptor, myeloid differentiation factor 88 (MyD88). Here, we dissected the role of MyD88 in parenchymal and bone marrow (BM)-derived cells in liver sensitization. Using chimeric mice with green fluorescent protein - expressing BM cells, we identified that P. acnes-induced liver inflammatory foci are of BM origin. Chimeras with MyD88-deficient BM showed no inflammatory foci after P. acnes or TLR2+TLR9 challenge, suggesting that recruitment of inflammatory cells to the liver required MyD88 expression in BM-derived cells. Further, selective MyD88 deficiency in parenchymal cells in mice with wild-type BM failed to prevent inflammatory cell infiltration. These results demonstrate that MyD88 in immune cells rather than in liver parenchymal cells plays an important role in inflammatory cell recruitment and liver injury.

Original languageEnglish
Pages (from-to)1342-1347
Number of pages6
JournalHepatology
Volume48
Issue number4
DOIs
Publication statusPublished - Oct 2008

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Myeloid Differentiation Factor 88
Bone Marrow
Liver
Propionibacterium acnes
Wounds and Injuries
Bone Marrow Cells
Toll-Like Receptors
Green Fluorescent Proteins
Lipopolysaccharides
Hepatocytes
Ligands

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)

Cite this

Bone marrow-derived immune cells mediate sensitization to liver injury in a myeloid differentiation factor 88-dependent fashion. / Hritz, I.; Velayudham, Arumugam; Dolganiuc, Angela; Kodys, Karen; Mandrekar, Pranoti; Kurt-Jones, Evelyn; Szabó, G.

In: Hepatology, Vol. 48, No. 4, 10.2008, p. 1342-1347.

Research output: Contribution to journalArticle

Hritz, I. ; Velayudham, Arumugam ; Dolganiuc, Angela ; Kodys, Karen ; Mandrekar, Pranoti ; Kurt-Jones, Evelyn ; Szabó, G. / Bone marrow-derived immune cells mediate sensitization to liver injury in a myeloid differentiation factor 88-dependent fashion. In: Hepatology. 2008 ; Vol. 48, No. 4. pp. 1342-1347.
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